Mortensen Martin Mørck, Høyer Søren, Lynnerup Anne-Sophie, Ørntoft Torben Falck, Sørensen Karina Dalsgaard, Borre Michael, Dyrskjøt Lars
Department of Molecular Medicine, Aarhus University Hospital, Brendstrupgårdsvej 100, DK-8200 Aarhus N, Denmark.
Department of Urology, Aarhus University Hospital, Brendstrupgårdsvej 100, DK-8200 Aarhus N, Denmark.
Sci Rep. 2015 Nov 2;5:16018. doi: 10.1038/srep16018.
Prostate cancer is a leading cause of cancer death amongst males. The main clinical dilemma in treating prostate cancer is the high number of indolent cases that confer a significant risk of overtreatment. In this study, we have performed gene expression profiling of tumor tissue specimens from 36 patients with prostate cancer to identify transcripts that delineate aggressive and indolent cancer. Key genes were validated using previously published data and by tissue microarray analysis. Two molecular subgroups were identified with a significant overrepresentation of tumors from patients with biochemical recurrence in one of the groups. We successfully validated key transcripts association with recurrence using two publically available datasets totaling 669 patients. Twelve genes were found to be independent predictors of recurrence in multivariate logistical regression analysis. SFRP4 gene expression was consistently up regulated in patients with recurrence in all three datasets. Using an independent cohort of 536 prostate cancer patients we showed SFRP4 expression to be an independent predictor of recurrence after prostatectomy (HR = 1.35; p = 0.009). We identified SFRP4 to be associated with disease recurrence. Prospective studies are needed in order to assess the clinical usefulness of the identified key markers in this study.
前列腺癌是男性癌症死亡的主要原因之一。治疗前列腺癌的主要临床困境在于大量惰性病例存在过度治疗的重大风险。在本研究中，我们对36例前列腺癌患者的肿瘤组织标本进行了基因表达谱分析，以鉴定区分侵袭性和惰性癌症的转录本。关键基因通过先前发表的数据和组织微阵列分析进行了验证。我们鉴定出两个分子亚组，其中一组中生化复发患者的肿瘤明显过多。我们使用两个总计669例患者的公开可用数据集成功验证了关键转录本与复发的关联。在多变量逻辑回归分析中，发现12个基因是复发的独立预测因子。在所有三个数据集中，复发患者的分泌型卷曲相关蛋白4（SFRP4）基因表达均持续上调。我们使用536例前列腺癌患者的独立队列显示，SFRP4表达是前列腺切除术后复发的独立预测因子（风险比=1.35；p=0.009）。我们确定SFRP4与疾病复发相关。需要进行前瞻性研究，以评估本研究中鉴定出的关键标志物的临床实用性。
